Schistosomiasis is a helminthic infection afflicting millions of people in developing countries. Although experimental evidence in laboratory animals and epidemiologic evidence in man suggest that protective immunity to schistosome infection can be induced by prior exposure, efforts to produce a defined vaccine against this parasite have been unsuccessful. Such a vaccine could significantly improve the overall health and economy in countries where schistosomiasis is endemic. We have recently developed a vaccination protocol against Schistosoma mansoni using crude nonliving antigens together with bacterial adjuvant that induces significant resistance to challenge infection in mice (Preliminary Results). This project proposes to extend that observation through 4 specific aims: (1) to refine and improve the efficacy of this model vaccination procedure in mice by determining the optimal combination of adjuvant, purified antigen and immunization schedule, (2) to analyze the specificity of this vaccine in terms of potential pathologic side-effects, target range and stage of the parasite against which it acts, (3) to investigate the immune mechanisms of resistance in this vaccine model, thus clarifying the relationship between method of antigen presentation and induction if protective immune responses, and (4) to evaluate the nonliving vaccine in other permissive rodent hosts, as a first step in modifying the protocol for use in higher animals. This work should culminate in the description of an optimum vaccination protocol against S. mansoni for use with dead antigens, whose mechanism of action and potential side-effects are fully understood in the mouse; this will be useful for testing the protective effects of defined antigens produced not only in the context of this proposal, but also by other investigators. Moreover, the fundamental requirements for modification of the protocol to other hosts will be defined The vaccination protocol that we have recently developed is one of the few effective experimental immunization procedures against S. mansoni using nonliving antigens to be described. It is hoped that systematic analysis of its action as described here will lay a firm groundwork for eventual development of a defined vaccine against schistosomiasis and provide vital information on the requirements for adaptation of an experimental murine vaccine to large animals and man, the ultimate goal of this research.